Cell replacement and visual restoration by retinal sheet transplants

Retinal diseases such as age-related macular degeneration (ARMD) and retinitis pigmentosa (RP) affect millions of people. Replacing lost cells with new cells that connect with the still functional part of the host retina might repair a degenerating retina and restore eyesight to an unknown extent. A unique model, subretinal transplantation of freshly dissected sheets of fetal-derived retinal progenitor cells, combined with its retinal pigment epithelium (RPE), has demonstrated successful results in both animals and humans. Most other approaches are restricted to rescue endogenous retinal cells of the recipient in earlier disease stages by a ‘nursing’ role of the implanted cells and are not aimed at neural retinal cell replacement. Sheet transplants restore lost visual responses in several retinal degeneration models in the superior colliculus (SC) corresponding to the location of the transplant in the retina. They do not simply preserve visual performance – they increase visual responsiveness to light. Restoration of visual responses in the SC can be directly traced to neural cells in the transplant, demonstrating that synaptic connections between transplant and host contribute to the visual improvement. Transplant processes invade the inner plexiform layer of the host retina and form synapses with presumable host cells. In a Phase II trial of RP and ARMD patients, transplants of retina together with its RPE improved visual acuity. In summary, retinal progenitor sheet transplantation provides an excellent model to answer questions about how to repair and restore function of a degenerating retina. Supply of fetal donor tissue will always be limited but the model can set a standard and provide an informative base for optimal cell replacement therapies such as embryonic stem cell (ESC)-derived therapy

An investigation of factors modulating wound healing after laser damage to the retina

SIGLEAvailable from British Library Document Supply Centre- DSC:DXN058875 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Untoward effects of high dose methylprednisolone therapy on blood-retinal barrier closure, retinal hole repair, and long-term scarring

Thirty-seven New Zealand Red rabbits were either dosed with methylprednisolone sodium succinate (MP, n=18) about 20 min before laser irradiation, or they were left untreated (n=19). Dosing with MP was tapered at 30, 30, 20, 20, and 10 mg/kg/day for five consecutive days. Retinas were irradiated with a multi-line argon laser to produce retinal injuries (grid of 16 lesions/eye) near hemorrhaging levels (285 mW/10msec, 290 μm retinal spot size). A variety of funduscopic and histologic assessments were made for hemorrhagic and non-hemorrhagic lesions from 10 min to 6 mo after injury. Fluorescein angiography showed that non-hemorrhagic control lesions stopped leaking at 3d post injury, but MP-treated lesions leaked for 2-4 days longer. After MP treatment, funduscopic lesion areas were similar to controls during the first 24 h then became smaller by 1 mo. After 1 mo, MP-treated lesions increased in area while controls became reduced. Histologic analysis showed no effect on reduction of neutrophils (PMN) in MP-treated lesions over controls at 3 hr. At 24 hr, retinal PMN values in hemorrhagic lesions of the MP group were elevated (p<0.05) while monocyte/macrophage counts were reduced (p<0.05) compared to control. At 4d, MP impeded replacement of lost retinal tissue, and contributed to retinal hole development at 1 mo followed by extensive enhancement of chorio-retinal scarring at 6 mo. In severe laser-induced retinal trauma, the immunosuppressive effects of high dose MP therapy contributed to a variety of untoward wound healing outcomes, thereby suggesting caution in its use to treat similar injuries in humans